UMLS:C0019829 - FACTA Search

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present article we describe a patient with AIDS and chylous ascites secondary to B-cell non Hodgkin's lymphoma. A 43 years old homosexual HIV-positive man. Complained of abdominal fullness, diarrhea and a rapidly increase in abdominal girth of 1 week duration. A diagnostic paracentesis was performed and revealed a milky fluid with high triglyceride levels. All blood tests and analysis of the peritoneal fluid with polymerase chain reaction for DNA sequence of broad-range bacterial Post Voiding Residual volume, Mycobacterium tuberculosis, Kaposi Sarcoma associated Herpes virus and Epstein Barr Virus were negative. CT scan did not demonstrate any evidence for cancer. An exploratory laparotomy was thus performed. A mass spreading along the mesenteric route to the omentum was found and a debulking resection was performed. The final pathology report was of diffuse, CD20-positive, CD3-negative, Epstein Barr Virus-negative, large B-Cell non Hodgkin's lymphoma. Subsequently, he underwent five cycles of CHOP (cyclofosfamide, doxorubicin, vincristin, prednison) chemotherapy with further partial regression of the abdominal tumour. Five months after the initial diagnosis of lymphoma, the patient relapsed and was treated with high-dose BEAM (carmustine, etoposide, cytosine, arabinoside, melphalan) chemotherapy followed by CD34 stem-cell transplantations salvage therapy. This notwithstanding, the patient died due to intestinal secondary to tumor relapse 2 months later.
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PMID:Chylous ascites secondary to B-cell non Hodgkin's lymphoma in a patient with the acquired immune deficiency syndrome (AIDS). 1799 72

The purpose of this article was to examine historic institutional autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for autologous transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of > or =2 x 10(6) CD34(+) cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34(+) cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected > or =2 x 10(6) CD34(+) cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34(+) cell yield and required less aphereses to collect > or =2 x 10(6) CD34(+) cells/kg. Mobilized, preapheresis, peripheral blood CD34(+) count correlated with first day apheresis yield (r = .877, P < .001) and 20 cells/microL was the minimum threshold needed for a successful day 1 collection. For the remobilization analysis we included patients from the whole database. A total of 269 of 1834 patients underwent remobilization using G/C, G-CSF, and/or GM-CSF, and G-CSF plus plerixafor. Only 23% of remobilized patients achieved > or =2 x 10(6) CD34(+) cells/kg and 29.7% failed to pool sufficient number of stem cells from both collections. Patients receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients remobilized with G-CSF who waited > or =25 days before remobilization had lower CD34(+) cell yield than those who waited < or =16 days, P = .023. Current mobilization regimens are associated with a substantial failure rate irrespective of underlying disease. Patients who fail initial mobilization are more likely to fail remobilization. These findings suggest that there is a need for more effective first-line mobilization agents.
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PMID:Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation. 1872 68

Phase I pharmacokinetic (PK) and pharmacodynamic (PD) studies in healthy volunteers demonstrated that plerixafor (AMD3100), a CXCR4 antagonist, administered either alone or with granulocyte colony-stimulating factor (G-CSF), resulted in dose-dependent mobilization of CD34(+) cells in the peripheral blood. The purpose of this study was to evaluate the safety and the PK and PD of plerixafor with G-CSF in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). This was a phase II, open-label, single-arm study conducted in 2 centers in Canada. Patients aged 18 to 70 years with NHL or MM eligible for autologous transplantation were eligible. A total of 22 patients (8 with NHL and 14 with MM) were enrolled in the study. The patients were given G-CSF (10 microg/kg/day subcutaneously [s.c.]) for 4 days in the morning and plerixafor 240 microg/kg s.c. on the evening before each day of apheresis. Apheresis was initiated 10 to 11 hours after each evening dose of plerixafor and after the morning dose of G-CSF. This regimen was repeated for up to 5 days or until > or = 5 x 10(6) CD34(+) cells/kg were collected. The objectives were to determine the safety and efficacy of plerixafor in patients with NHL and MM, and the PK and PD of a single 240-microg/kg dose of plerixafor administered after 4 days of G-CSF mobilization in these patients. The median absolute peripheral blood CD34(+) cell count increased from 24.0 cells/microL before plerixafor administration to 75.0 cells/microL before the first apheresis (10 to 11 hours after treatment with plerixafor). The median number of CD34(+) cells collected in a median of 1 day was 5.7 x 10(6) cells/kg in the patients with NHL and 12.0 x 10(6) cells/kg in those with MM. All patients underwent transplantation with prompt and durable engraftment. The PK profile of plerixafor was characterized in 13 patients (5 with NHL and 8 with MM). Overall, the PK parameters were comparable in the patients with NHL and those with MM. Plerixafor was rapidly absorbed after s.c. administration with no observable lag time, with peak plasma concentrations occurring 0.5 hour after administration in most patients. Plerixafor was rapidly cleared, with a median terminal half-life of 4.6 hours. The median maximum increase in the number of circulating cells from baseline was 4.2-fold (range, 3.0- to 5.5-fold), with the maximum fold increase occurring approximately 10 hours after plerixafor injection for all patients. The plerixafor PK and PD profiles in the study patients were consistent with those in healthy volunteers and support the current dosing regimen and timing of apheresis. Plerixafor was safe and effective in mobilizing CD34(+) cells for transplantation.
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PMID:Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma. 1913 41

The aim of this study was to evaluate the apoptotic damage to bone marrow cells caused by three chemotherapy regimens for advanced Hodgkin's lymphoma, ABVD, COPPEBVCAD and BEACOPP, which were randomly administered in the HD 2000 GISL trial. Bone marrow mononuclear cells (BMMCs) stained with anti-CD34 antibody and Annexin V, were evaluated by flow cytometry before starting chemotherapy, 30 days after completing chemotherapy and after 6 months. Results are expressed as the percentages of BMMCs positive to anti-CD34, to Annexin V or to both. Fourteen patients treated with ABVD, 11 with COPPEBVCAD and 13 with BEACOPP were evaluated before and 30 days after treatment. Late assessments were made in 6, 7 and 8 of them, respectively. No differences were found among the pretherapeutic flow cytometry findings in relation to the staging characteristics (marrow involvement included). All the regimens increased the apoptotic fraction of the whole mononuclear bone marrow cells (COPPEBVCAD did so significantly) and increased the CD34+ compartment (with significant early differences after ABVD and BEACOPP, tending to late persistence for ABVD, only). All the regimens increased the apoptotic CD34+ cells within the whole BMMC population (significantly after BEACOPP), although with a general trend to decrease in their percentage within the CD34+ compartment over time, even after the most dose-dense regimens. Based on the variations induced in the apoptotic fraction of all mononuclear and CD34+ cells, ABVD was the least toxic regimen and COPPEBVCAD the most toxic one.
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PMID:Bone marrow stem cell damage after three different chemotherapy regimens for advanced Hodgkin's lymphoma. 1928 5

Angiogenic switch marks the beginning of tumor's strategy to acquire independent blood supply. In some subtypes of non-Hodgkin's lymphomas, higher local vascular endothelial growth factor (VEGF) expression correlates with increased microvessel density. However, this local VEGF expression is higher only in tumors with elevated expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. Several studies have indicated that VEGF receptors are also targeted by Tat protein from the HIV-1-infected cells. Given the similarity of the basic region of Tat to the angiogenic factors (basic fibroblast growth factor, VEGF), Tat mimics these proteins and binds to their receptors. We evaluated the role of HIV-1 Tat in regulating the level of VEGF expression and microvessel density in the AIDS-related diffuse large B-cell (DLBCL) and Burkitt lymphomas (BL). By luciferase assay, we showed that VEGF promoter activity was downregulated in vitro in cells transfected with Tat. Reduced VEGF protein expression in primary HIV-1 positive BL and DLBCL, compared to the negative cases, supported the findings of promoter downregulation from the cell lines. Microvascular density assessed by CD34 expression was, however, higher in HIV-1 positive than in HIV-1 negative tumors. These results suggest that Tat has a wider angiogenic role, besides the regulation of VEGF expression. Thus, targeting Tat protein itself and stabilizing transient silencing of VEGF expression or use of monoclonal antibodies against their receptors in the AIDS-associated tumors will open a window for future explorable pathways in the management of angiogenic phenotypes in the AIDS-associated non-Hodgkin's lymphomas.
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PMID:HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas. 1966 99

Plerixafor is a novel small molecule that inhibits CXCR4 binding to SDF-1, an interaction that is a principal regulator of hematopoietic stem cell trafficking. Phase I studies demonstrated that a single plerixafor hydrochloride dose results in a marked increase in white blood cell count and circulating CD34(+) stem cells. Subsequent single-arm and randomized clinical trials have established the efficacy of plerixafor for autologous stem cell mobilization, both combined with granulocyte colony-stimulating factor (G-CSF) and as a single agent. In December 2008 the FDA approved plerixafor in combination with G-CSF for autologous stem cell mobilization in patients with non-Hodgkin lymphoma or multiple myeloma. Plerixafor is also effective for stem cell mobilization in patients with Hodgkin lymphoma and in those who have failed a prior cytokine or chemotherapy mobilization. Preliminary studies of plerixafor in sibling donors demonstrate its efficacy for allogeneic stem cell mobilization, without any observed increase in graft failure or graft versus host disease. This review will summarize clinical trials, current use for autologous stem cell mobilization and future directions for plerixafor.
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PMID:Plerixafor hydrochloride: a novel agent for the mobilization of peripheral blood stem cells. 1983 27

In a phase 3 multicenter, randomized, double-blinded, placebo-controlled study of 298 patients with non-Hodgkin lymphoma (NHL), granulocyte colony-stimulating factor (G-CSF) plus plerixafor increased the proportion of patients who mobilized >or=5 x 10(6) CD34(+) hematopoietic stem cells (HSCs)/kg compared with placebo plus G-CSF (P < .001). Patients in either study arm who failed mobilization (< 0.8 x 10(6) CD34(+) cells/kg in 2 collections or <2 x 10(6) CD34(+) cells/kg in 4 collections) were eligible to enter the opened-label rescue protocol. Following a 7-day minimum rest period, these patients received G-CSF (10 microg/kg/day) for 4 days, followed by daily plerixafor (0.24 mg/kg) plus G-CSF and apheresis for up to 4 days. Of the 68 patients failing initial mobilization (plerixafor, n = 11; placebo, n = 57), 62 patients (91%) entered the rescue procedure (plerixafor, n = 10; placebo, n = 52). Four of 10 patients (40%) from the plerixafor group and 33 of 52 (63%) from the placebo group mobilized sufficient CD34(+) cells (>or= 2 x 10(6) cells/kg) for transplantation from the rescue mobilization alone (P = .11). Engraftment of neutrophils (11 days) and platelets (20 days) was similar to that in patients who did not fail initial mobilization, and all patients had durable grafts at the 12-month follow-up. Common plerixafor-related adverse events (AEs) included mild gastrointestinal (GI) effects and injection site reactions. There were no drug-related serious AEs. These data support that plerixafor plus G-CSF can safely and effectively remobilize patients with NHL who have failed previous mobilization.
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PMID:Successful stem cell remobilization using plerixafor (mozobil) plus granulocyte colony-stimulating factor in patients with non-hodgkin lymphoma: results from the plerixafor NHL phase 3 study rescue protocol. 1989 82

As more efficient agents for stem cell mobilization are being developed, there is an urgent need to define which patient population might benefit from these novel drugs. For a precise and prospective definition of "poor mobilization" (PM), we have analyzed the efficiency of mobilization in patients intended to receive autologous transplantation at our center in the past 6 years. Between January 2003, and December 2008, 840 patients with the following diagnoses were scheduled to undergo leukapheresis: multiple myeloma (MM, n = 602) and non-Hodgkin lymphoma (NHL, n= 238). Most patients mobilized readily: close to 85% of the patients had a level of 20/microL to >500/microL of CD34(+) cells at the peak of stimulation. Of the 840 patients, 129 (15.3%) were considered to be PMs, defined as patients who had a peak concentration of <20/microL of CD34(+) cells upon stimulation with granulocyte-colony stimulating factor (G-CSF) subsequent to induction chemotherapy appropriate for the respective disease. Among them, 38 (4.5%) patients had CD34(+) levels between 11 and 19/microL at maximum stimulation, defined as "borderline" PM, 49 (5.8%) patients had CD34(+) levels between 6 and 10/microL, defined as "relative" PM, and 42 patients (5%) with levels of <5/microL, defined as "absolute" PM. There was no difference in the incidence of PM between patients with MM versus those with NHL. Sex, age, body weight (b.w.) and previous irradiation therapy did not make any significant difference. Only the total number of cycles of previous chemotherapy (P = .0034), and previous treatment with melphalan (Mel; P = .0078) had a significant impact on the ability to mobilize. For the good mobilizers, the median time to recovery of the white blood cells (WBCs) to 1.0/nL or more was 13 days with a range of 7 to 22 days, whereas for the PM group it was 14 days with a range of 8 to 37 days. This difference was statistically not significant. The median time to recovery of the platelets counts to an unmaintained level of >20/nL was 11 days with a range of 6 to 17 days for the good mobilizers, whereas for the PM it was 11 days with a range of 7 to 32 days. Again, this difference was not significant. The majority of the patients today intended for autologous transplantations were able to mobilize readily. As long as > or =2.0 x 10(6) of CD34(+) cells/kg b.w. have been collected, PM was not associated with inferior engraftment.
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PMID:Poor mobilization of hematopoietic stem cells-definitions, incidence, risk factors, and impact on outcome of autologous transplantation. 1992 76

Autologous hematopoietic stem cell (HSC) transplantation is a treatment strategy for restoring normal hematopoietic function in patients with select hematologic malignancies. The number of CD34(+) cells available for transplantation has been reported to be the strongest predictor of transplantation success, as measured by rapid and durable hematopoietic recovery. Currently, granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus chemotherapy are the most commonly used methods for stem cell mobilization. Unfortunately, 5-30% of patients do not respond to these agents. Plerixafor is a new HSC mobilizing drug that antagonizes the binding of chemokine stromal-cell-derived factor-1alpha (SDF-1alpha) to CXC chemokine receptor 4 (CXCR4). It is indicated in combination with G-CSF to mobilize HSC to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Results of clinical trials have shown that plerixafor plus G-CSF allow for the collection of a high yield of HSC with fewer apheresis sessions in patients with NHL and MM. Plerixafor has also shown promising results in small studies enrolling patients with Hodgkin's lymphoma. Moreover, for patients who fail G-CSF mobilization alone, plerixafor with G-CSF may be useful as a salvage mobilization strategy. Overall, plerixafor has been generally well tolerated with adverse effects classified as mild to moderate. The most common adverse effects reported in randomized clinical trials were injection site reactions and diarrhea, with approximately 33% of patients experiencing these effects. To our knowledge, clinical trials comparing G-CSF plus plerixafor with G-CSF plus chemotherapy and cost-effectiveness analyses have not been published; therefore, questions remain regarding the optimal role of plerixafor in the clinical practice setting.
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PMID:Plerixafor: a peripheral blood stem cell mobilizer. 2041 99

Cytogenetic abnormalities seen at presentation of acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/ LBL) are associated with distinct clinical and hematologic disease entities. T-ALL/LBL are morphologically indistinguishable from those of B-ALL/LBL. An abnormal kariotype is found in 50-70% of cases of T-ALL/LBL. We present a 35-year old male patient with T-ALL/LBL and t(8;14)(q24;q11.2). Our patient presented with B-symptoms, bulky mediastinal disease and CNS infiltration. Bone marrow was morphologically normal and cytogenetically without clonal aberrations. Cytological findings of the supraclavicular lymph node showed numerous CD3 positive (100%) and CD2 positive (88%) lymphoblasts, negative for CD34 and CD10. Flow cytometry of lymph node revealed T cell phenotype of immature cells: CD45+CD2+CD5+CD7+CD4+CD8+CD3cyt +CD3TdT+CD10-CD34-HLAD/DR-. Cytogenetic analysis of lymph node showed translocation t(1;4)(p32;p12), t(8;14)(q24;q11.2). Southern blot analysis of extracted DNA from the supraclavicular lymph node demonstrated clonal rearrangement of the T cell antigen receptor (TCR/J) gene (region Vb+Jb2). Based on these findings, diagnosis of T lymphoblastic non Hodgkin lymphoma was established. Cerebrospinal fluid analysis showed CNS infiltration with 49% lymphoblasts positive for CD4 and CD8. The disease progressed rapidly with poor response to therapy. T-ALL/LBL with an unusual t(8;14)(q24;q11.2) is a very rare hematologic disorder with rapid disease progression and poor response to conventional therapy because of frequent central nervous system involvement and early relapses.
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PMID:T-lymphoblastic lymphoma with an unusual t(8;14)(q24;q11)--case report. 2043 60

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